Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0204853
Title: Regulation of the NRF2 transcription factor by andrographolide and organic extracts from plant endophytes
Authors: Wen Wong D.P.
Ng M.Y. 
Leung J.Y.
Boh B.K. 
Lim E.C.
Tan S.H.
Lim S.
Seah W.H.
Hu C.Z. 
Ho B.C.
Ng D.H.P.
Hagen T. 
Keywords: andrographolide
cullin
cullin 3
kelch like ECH associated protein 1
protein RBX1
RING finger protein
sulforaphane
transcription factor Nrf2
unclassified drug
andrographolide
carrier protein
CUL3 protein, human
cullin
diterpene
KEAP1 protein, human
kelch like ECH associated protein 1
NFE2L2 protein, human
plant extract
protein binding
RBX1 protein, human
transcription factor Nrf2
Article
binding affinity
Calymperes erosum
Campylopus serratus
densitometry
Dicranopteris linearis
endophyte
enzyme activity
fern
human
human cell
moss
nonhuman
Ophioglossum reticulatum
Philonotis thwaitesii
Phlegmariurus phlegmaria
protein binding
protein degradation
protein expression
protein function
protein interaction
protein localization
protein processing
protein stability
Psilotum nudum
Pyrrosia piloselloides
Taenitis blechnoides
ubiquitination
Vesicularia dubyana
binding site
chemistry
drug effect
endophyte
gene expression regulation
HEK293 cell line
metabolism
secondary metabolism
Binding Sites
Bryophyta
Carrier Proteins
Cullin Proteins
Diterpenes
Endophytes
Ferns
Gene Expression Regulation
HEK293 Cells
Humans
Kelch-Like ECH-Associated Protein 1
NF-E2-Related Factor 2
Plant Extracts
Protein Binding
Secondary Metabolism
Ubiquitination
Issue Date: 2018
Publisher: Public Library of Science
Citation: Wen Wong D.P., Ng M.Y., Leung J.Y., Boh B.K., Lim E.C., Tan S.H., Lim S., Seah W.H., Hu C.Z., Ho B.C., Ng D.H.P., Hagen T. (2018). Regulation of the NRF2 transcription factor by andrographolide and organic extracts from plant endophytes. PLoS ONE 13 (10) : e0204853. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0204853
Abstract: The transcription factor NF-E2 Related Factor-2 (NRF2) is an important drug target. Activation of NRF2 has chemopreventive effects in cancer and exerts beneficial effects in a number of diseases, including neurodegenerative diseases, inflammatory diseases, hepatosteatosis, obesity and insulin resistance. Hence, there have been great efforts to discover and characterize novel NRF2 activators. One reported NRF2 activator is the labdane diterpenoid andrographolide. In this study, we identified the mechanism through which andrographolide activates NRF2. We showed that andrographolide inhibits the function of KEAP1, a protein that together with CUL3 and RBX1 forms an E3 ubiquitin ligase that polyubiquitinates NRF2. Andrographolide partially inhibits the interaction of KEAP1 with CUL3 in a manner dependent on Cys151 in KEAP1. This suggests that andrographolide forms Michael acceptor dependent adducts with Cys151 in KEAP1 in vivo, leading to inhibition of NRF2 ubiquitination and consequently accumulation of the transcription factor. Interestingly, we also showed that at higher concentrations andrographolide increases NRF2 protein expression in a Cys151 independent, but likely KEAP1 dependent manner, possibly through modification of other Cys residues in KEAP1. In this study we also screened secondary metabolites produced by endophytes isolated from non-flowering plants for NRF2-inducing properties. One of the extracts, ORX 41, increased both NRF2 protein expression and transcriptional activity markedly. These results suggest that endophytes isolated from non-flowering or other plants may be a good source of novel NRF2 inducing compounds. © 2018 Wong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165895
ISSN: 19326203
DOI: 10.1371/journal.pone.0204853
Appears in Collections:Elements
Students Publications
Staff Publications

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
10_1371_journal_pone_0204853.pdf7.34 MBAdobe PDF

OPEN

NoneView/Download

SCOPUSTM   
Citations

9
checked on Jun 19, 2021

Page view(s)

103
checked on Jun 11, 2021

Download(s)

1
checked on Jun 11, 2021

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.